Plasma p-Tau217 improves diagnostic accuracy and clinician confidence in cognitive disorder classification

The clinical utility of plasma phosphorylated tau 217 (p-tau217) levels as a diagnostic tool for cognitive disorders in real-world settings remains uncertain. In this cross-sectional retrospective study, 738 consecutive subjects presenting with cognitive complaints at a memory clinic underwent diagnostic evaluation incorporating plasma p-tau217 alongside standard clinical assessments (“Tier 2”: routine neuroimaging and cognitive testing) and advanced biomarker testing (“Tier 1”: amyloid PET imaging or CSF analysis). Diagnostic impact and confidence were assessed using clinician surveys. Incorporating plasma p-tau217 into the routine “Tier 2” diagnostic workup significantly influenced clinical decision-making, leading to diagnostic revisions in 30.2% of cases and improving overall diagnostic confidence from 65.1% to 79.4%.

Plasma p-tau217 demonstrated high diagnostic accuracy for Alzheimer’s disease (AD), with a sensitivity of 0.88 and specificity of 0.84. Notably, its specificity was superior to “Tier 2” diagnoses, whereas its sensitivity did not differ significantly. Plasma p-tau217 also exhibited non-inferior performance to “Tier 1” approaches in the diagnostic distribution of AD, though with marginally lower diagnostic confidence. For non-AD diagnoses, plasma p-tau217 significantly impacted the classification of synucleinopathies and performed comparably to “Tier 1” methods. In conclusion, plasma p-tau217 meaningfully impacted diagnostic precision and confidence in subjects presenting to a real-world memory clinic, offering a minimally invasive, cost-effective, and accessible alternative to state-of-the-art examinations. As the global population ages and cognitive disorders become more prevalent, the integration of plasma p-tau217 into routine practice has the potential to streamline diagnostic workflows and enhance the efficient utilization of medical resources.